Solvent-Induced Chirality Switching in the Enantioseparation of Hydroxycarboxylic Acids with a Quaternary Stereogenic Center

Abstract

The enantiomer separation of three isomeric hydroxycarboxylic acids with a quaternary stereogenic center via diastereomeric salt formation with (1R,2S)-2-amino-1,2-diphenylethanol was demonstrated. Racemic acid 1, with a quaternary chiral center at the β-position, was separated with nearly ideal efficiency. The stereochemistry of acids 2 and 3 incorporated in the less-soluble salts was reversed depending on the recrystallization solvents, and both enantiomers were accessible. The mechanism of this chirality switching was discussed based on the crystal structures of the less-soluble diastereomeric salts; the solvation of the salt with an alcohol molecule changed the hydrogen-bonding network and its stability.